Epstein-Barr Virus
Epstein-Barr virus (EBV) is a human γ-herpesvirus
that is able to establish a long-term, latent infection in human B cells
for the life of the host.
http://cullenlab.duhs.duke.edu/research/ebv/
Uit een zeer kleinschalige studie van
Dr. Lerner,
dr. Glaser en collega's blijkt dat
bij een deel van de patiënten met CVS sprake is van langdurige productie van
antilichamen
tegen specifieke eiwitten die door het Epstein-Barr virus aangemaakt worden:
- DNA polymerase:
een eiwit dat essentieel is om het DNA van het virus te vermenigvuldigen en
- deoxyuridine triphosphate nucleotidohydrolase (dUTPase):
een eiwit dat genetische foutjes bij reproductie minimaliseert.
Volgens Lerner en collega's zijn deze antilichamen specifiek voor een
abortief-lytische EBV-infectie (géén volledige replicatie, wél apoptose van gastheercellen).
Lerner heeft deze hypothese in onderstaand artikel beschreven (klik op afbeelding):
Het positieve van deze studie is het feit dat patiënten langer gevolgd werden.
Jammer genoeg werd slechts een kleine groep CVS-patiënten (6) onderzocht.
In een presentatie uit 2011 besteedde Lerner uitgebreid aandacht aan zijn theorie:
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Citaten uit de studie:
The six CFS patients were identified as;
Group A EBV subset (five patients), and
Group B (one patient) who was co-infected with Borrelia burgdorferi [2].
...
The preliminary data demonstrate that
there is a prolonged elevated antibody level against a subset of patients with CFS,
suggesting that this antibody panel could be used to identify such patients.
We published the first evidence that the EBV-encoded dUTPase
is able to induce immune dysregulation in vitro
as demonstrated by its effect on the replication of PBMCS and
the production of several different proinflammatory cytokines
including IL-1β, TNF-α, IL-6, IL-8 and IL-10 [13].
...
In this study we demonstrate that
there is a statistically significant increase in antibody levels to
EBV EA-D complex, EBV-encoded dUTPase and EBV-encoded DNA polymerase
in repetitive longitudinal serum samples obtained from six CFS Group A EBV subset patients
studied over a consecutive period of 13–16 months
who were treated with valacyclovir when compared to a control group.
...
Both the Fluge [38] and Strayer studies [39] are consistent with the herpesvirus' CFS paradigm proposed by our group,
and supported by the presence of elevated serum antibody to encoded proteins EBV DNA polymerase and EBV dUTPase reported here.
...
CFS patients have impaired NK cell function and numbers [17].
These NK changes may be either primary genetic, or
due to herpesvirus abortive lytic replication, we describe.
...
Patients with Group A CFS with subsets CMV or HHV6 do not respond to valacyclovir [2].
Likewise, Group B CFS patients with unrecognized co-infections do not respond to valacyclovir [2].
Antibody to Epstein-Barr virus deoxyuridine triphosphate nucleotidohydrolase and deoxyribonucleotide polymerase in a chronic fatigue syndrome subset.
PLoS ONE. 2012;7(11): e47891. doi:10.1371/journal.pone.0047891.
Lerner AM, Ariza ME, Williams M, Jason L, Beqaj S, Fitzgerald JT, Lemeshow S, Glaser R.
Methods
Antibody to E
BV viral capsid antigen (VCA) IgM, EBV Diffuse Early Antigen EA(D), and
neutralizing antibodies against EBV-encoded DNA polymerase and EBV-encoded dUTPase
were assayed serially approximately every three months for 13–16 months
from sera obtained from patients with CFS (6) and
from sera obtained from twenty patients who had no history of CFS.
Results
Antibodies to EBV EA(D) and
neutralizing antibodies against
the encoded-proteins EBV DNA polymerase and
deoxyuridine triphosphate nucleotidohydrolase (dUTPase)
were present in the EBV subset CFS patients.
Of the sera samples' obtained from patients with CFS
93.9% were positive for EA(D),
while 31.6%
of the control patients were positive for EBV EA(D).
Serum samples were
positive for
neutralizing antibodies
against the EBV-encoded dUTPase (23/52; 44.2%) and
DNA polymerase (41/52; 78.8%)
in EBV subset CFS patients,
but negative in sera of controls.
Conclusions
There is
prolonged elevated antibody level
against the encoded proteins
EBV dUTPase and
EBV DNA polymerase
in a subset of CFS patients,
suggesting that
this antibody panel
could be used
to identify these patients,
if these preliminary findings
are corroborated by studies
with a larger number of
EBV subset CFS patients.
http://www.plosone.org/article/fetchObjectAttachment.action;
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